Hydrocarbon chain length-dependent antagonism of acylcarnitines to the depressant effect of lysophosphatidylcholine on cardiac sodium current.

Amphiphilic lipid metabolites, including lysophosphatidylcholine (lysoPC) and long-chain acylcarnitine, accumulate in an ischemic myocardium and exert deleterious effects on membrane function. The effects of short-chain (3-carbon-chain, C3), medium-chain (C6 and C8), long-chain (C16) acylcarnitines, and lysoPC on the sodium current (INa) of isolated guinea-pig ventricular cells and on membrane fluidity and [14C]lysoPC uptake in cultured mouse embryo ventricular cells were examined. Guinea-pig ventricular cells were superfused with low-Na+(60 mM) Tyrode solution at a temperature of 32-33 degrees C. Ca2+ and K+ currents were blocked by external Co2+(3 mM) and internal Cs+(140 mM), respectively. Neither propionylcarnitine (PpC, C1) nor hexanoylcarnitine (HxoC. C6) at concentrations of 50, 100, 500 microM affected the amplitude of peak LNa, evoked by depolarizing pulses (0.5 Hz) to -20 mV from a holding potential of -100 mV. Octanoylcarnitine (OcoC, C8) (50 and 100 microM) did not alter the amplitude of peak INa while the highest concentration (500 microM) did inhibit it by 7.7 +/- 3.0% (mean +/- S.E., n = 6) significantly. Palmitoylcarnitine (PamC, C16) (1, 5, and 50 microM), decreased the amplitude of peak INa by 16.6 +/- 5.2% (n = 5), 36.1 +/- 4.3% (n = 11), and 52.7 +/- 8.8% (n = 4), respectively. LysoPC (50 microM) irreversibly depressed INa within 30 +/- 4 seconds (n = 4), and cell contracture occurred. If short- and medium-chain acylcarnitines would prevent the depressant effects of lysoPC on INa was then investigated. In the presence of PpC (100 microM) or HxoC (100 microM), the effects of lysoPC (either depression of INa or development of cell contracture) were not observed, while OcoC (100 microM) did not prevent any of these effects of lysoPC. In contrast, PpC and HxoC failed to prevent the reduction of INa caused by PamC. From these findings and membrane fluidity and [14C]lysoPC uptake studies, it was concluded that PpC exerts the protective effect by preventing the incorporation of lysoPC into phospholipid bilayers, and that short-chain acylcarnitine has a potent anti-amphiphilic effect against the amphipathic insults caused by lysoPC, whereas long-chain acylcarnitine had a potent amphiphilic effect; medium-chain acylcarnitine appeared to share both characteristics.